SIGLEC1 FACILITATES MACROPHAGE-CD8+ T CELL INTERACTIONS AND CORRELATES WITH CANCER IMMUNOTHERAPY RESPONSE

Ibanez Molero, S.; Coccimiglio, M.; Olivia Springer, B.; Bowien de Ruiter, M.; Clayton, G.; Wijnen, S.; Blank, C.; Labots, M.; de Gruijl, T.; van Kooyk, Y.

doi:10.64898/2026.07.09.737484

bioRxiv · 10.64898/2026.07.09.737484

SIGLEC1 FACILITATES MACROPHAGE-CD8+ T CELL INTERACTIONS AND CORRELATES WITH CANCER IMMUNOTHERAPY RESPONSE

Ibanez Molero, S.·Coccimiglio, M.·Olivia Springer, B.·Bowien de Ruiter, M.·Clayton, G.·Wijnen, S.·Blank, C.·Labots, M.·de Gruijl, T.·van Kooyk, Y.

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Abstract

Antigen-presenting cell (APC) interactions with cytotoxic T cells are critical for anti-tumour immunity and response to immune checkpoint blockade (ICB), yet context-specific regulators in the tumour microenvironment remain not fully defined. Here we identify the lectin receptor SIGLEC1 as a key mediator of macrophage-T cell interactions in human melanoma. In a well-characterized patient cohort, SIGLEC1 was selectively upregulated in inflammatory macrophages physically associated with activated/exhausted CD8 T cells. Imaging and functional analyses revealed that SIGLEC1 accumulates at the macrophage-T cell interface and promotes cell clustering. SIGLEC1 ligands were enriched on activated T cells, and their blockade reduced cytotoxic cytokine production ex vivo. Single-cell (spatial) transcriptomics across independent ICB-treated melanoma cohorts showed that SIGLEC1 macrophages localize near CD8 T cells and are enriched in responders, where they also associate with T cells expressing activation/exhaustion markers. These findings define a SIGLEC1-dependent macrophage-T cell niche linked to effective immunotherapy.

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Ibanez Molero, S., Coccimiglio, M., Olivia Springer, B., Bowien de Ruiter, M., Clayton, G., Wijnen, S., Blank, C., Labots, M., de Gruijl, T., van Kooyk, Y.. 2026-07-15. SIGLEC1 FACILITATES MACROPHAGE-CD8+ T CELL INTERACTIONS AND CORRELATES WITH CANCER IMMUNOTHERAPY RESPONSE. https://doi.org/10.64898/2026.07.09.737484

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